Study reveals trigonelline as a treatment for age-related mitochondrial dysfunction

Recent research published in journals natural metabolism reported low nicotinamide adenine dinucleotide (NAD) levels.⁺) and mitochondrial dysfunction observed during sarcopenia and skeletal muscle aging were functionally linked to serum levels of the natural alkaloid trigonelline.

study: Trigonelline is NAD⁺ Precursors that improve muscle function during aging and reduce sarcopenia in humans. Image credit: BigBlueStudio/Shutterstock.com

background

Sarcopenia is the age-related decline of skeletal muscle due to muscle fiber wasting, resulting in impaired muscle fiber contraction, decreased mobility, and disability.

Clinical symptoms of sarcopenia include loss of muscle mass and consequent loss of gait speed and muscle strength. Research has shown that mitochondrial dysfunction plays an important role in the development of sarcopenia.

The muscle aging phenotype is caused by factors such as decreased mitochondrial biogenesis, decreased cellular respiration and adenosine triphosphate (ATP) production, and altered mitochondrial dynamics.

Recent research has focused on understanding the role of systemic factors such as proinflammatory cytokines, circulating anabolic amino acids, and fluctuations in lipid, vitamin, and glucose metabolism in influencing mitochondrial function and influencing muscle strength. .

low levels of NAD⁺ Recently, mitochondrial dysfunction was identified as one of the hallmarks of muscle aging and sarcopenia.

However, whether NAD levels decrease⁺ The relevance of circulating molecular markers that can be used as clinical biomarkers remains unclear.

About research

In this study, researchers investigated whether serum vitamin B or kynurenine metabolomic levels differ in sarcopenic patients compared to healthy individuals to determine systemic changes associated with NAD.⁺ Metabolic changes and mitochondrial dysfunction.

They are⁺ Derived from vitamin B₃ It is a precursor and essential cofactor for biological and cellular metabolism.

In mammals, NAD⁺ from dietary precursors such as nicotinamide mononucleotide and nicotinamide riboside via the nicotinamide riboside kinase pathway to tryptophan such as nicotinic acid or niacin via the nicotinic acid phosphoribosyltransferase-dependent place-handler pathway. It can be produced from nicotinamide.

Rodent studies also support findings from human studies that NAD declines with aging in skeletal muscle.⁺ level.

The study included participants aged 60 and older with sarcopenia and an equal number of age-matched healthy controls. Muscle biopsy samples were collected from all participants for analysis. A digital dynamometer was used to measure grip strength, and dual-energy X-ray absorptiometry was used to measure limb lean body mass index.

A 24-hour recall method was employed to assess dietary intake, and all reported household portion sizes of food and beverages were converted to grams using a standard reference.

Ribonucleic acid (RNA) sequencing was performed using vastus lateralis biopsies, and the resulting genetic dataset was used for pathway analysis.

Furthermore, the concentration of NAD is⁺ NAD from tissue samples was quantified enzymatically, and liquid chromatography-mass spectrometry was used for high-resolution analysis of NAD.⁺ metabolome of alive samples and cells.

A wide range of cellular assays were performed to assess cell death, mitochondrial function, nicotinic acid phosphoribosyltransferase gene knockdown, G protein-coupled receptor agonism, and NAD stability.⁺ precursor.

Muscle tissues from biopsies were also stained for histological evaluation to observe muscle structure.

Knockdown studies of nicotinic acid phosphoribosyltransferase were performed using a rodent model, and RNA extracts from rodent tissues were used for quantitative polymerase chain reaction (qPCR) and immunoblot assays.

result

As a result, although there is vitamin B,₃ The metabolites and other metabolites analyzed in the study showed no changes associated with sarcopenia, and sarcopenic patients had lower levels of trigonelline, a natural alkaloid produced by mammals and plants.

Appendicular lean body mass index, gait speed and grip strength measurements showed a correlation between muscle mass and deltoid muscle levels. Additionally, serum trigonelline levels were found to be associated with NAD levels.⁺ in skeletal muscle.

Pathway enrichment studies from rodent tissues also showed that a number of signaling and metabolic pathways, such as the mitochondrial oxidative phosphorylation pathway, were positively correlated with serum trigonelline levels.

Dietary intake analysis found that caffeine intake was not associated with changes in serum trigonelline levels. Nevertheless, it has been shown that fiber and folic acid intake can influence circulating levels of trigonelline.

Changes in vitamin B₃ Also, intake does not seem to affect the association between muscle strength and trigonelline levels. These findings suggested that trigonelline is a new metabolite that can be used as a biomarker to assess her NAD.⁺ levels, mitochondrial metabolism, and muscle strength.

conclusion

In summary, this study investigated the association between levels of the vitamin B3 metabolome and NAD+ levels, muscle mass, and mitochondrial dysfunction associated with sarcopenia through RNA-seq, histological analysis, animal experiments, and numerous assays. did.

The results showed no association between sarcopenic characteristics and vitamin B.₃ Metabolome finds that low levels of trigonelline, a natural alkaloid found in humans, are associated with decreased NAD⁺ levels, muscle mass loss, and mitochondrial dysfunction.